In certain instances numerous pharmacologenetic disorders in man cause individuals to react very differently to the same dose of the same drug. The teratogenic, carcinogenic or toxic effects of certain drugs and other foreign compounds (xenobiotics) may also reflect important genetically mediated differences between individuals. Accordingly, this laboratory has developed experimental model systems for studying drug metabolism in a colony of inbred strains of mice. We have determined that the genetically mediated presence or absence of induction of aryl hydrocarbon (benzo(a)pyrene) hydroxylase activity is highly correlated with the N-hydroxylation of N-acetylarylamines in the livers of C57BL/6N and DBN/2N treated with 3- methylcholanthrene, beta-naphtoflavone, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, and sodium pentobarbital. The extent of hepatotoxicity caused by acetaminophen (p-hydroxyacilamilide) administration is also highly associated with the aryl hydrocarbon hydroxylase activity. This genetic model offers a useful probe for demonstrating difference in the rate of formation of certain drug-induced birth defects.